Current and emerging fixed combination therapies in glaucoma: a safety and tolerability review

ABSTRACT

Introduction

Fixed dose combinations (FCs) represent a potentially valuable treatment strategy in glaucoma management. Fixed combinations not only improve adherence by reducing the medication burden, but also decrease the total amount of potentially deleterious preservatives an eye is exposed to.

Areas covered

We provide a critical review of selected evidence on both the safety and tolerability of presently available and emerging glaucoma FCs. There is convincing short-term safety and tolerability evidence on intraocular pressure (IOP)-lowering FCs compared to that of monotherapies and, to a lesser degree, to that of concomitant, equivalent combination therapies. In contrast, there is a scarcity of trials evaluating the long-term efficacy and safety of glaucoma FCs and no conclusive data on the reduction of adverse events with FCs.

Expert opinion

It is vital for clinicians to carefully weigh the efficacy, safety, tolerability, and adherence of IOP-lowering FCs. Given the number of currently available and emerging FC therapy options in glaucoma, as well as the complexities of incorporating them in the various combination therapy regimens, successful stepwise therapy remains often elusive.

KEYWORDS:

• Glaucoma
• ocular hypertension
• fixed combinations
• intraocular pressure
• glaucoma treatment
• IOP

Article highlights

• Lifelong, successful medical therapy in glaucoma remains a major clinical challenge.

• Glaucoma FCs involving 2 or 3 agents within the same formulation possess similar, or complimentary IOP-lowering mechanisms of action. They exhibit diverse dosing, safety, and tolerability profiles and aim to provide adequate 24-hour IOP control.

• Glaucoma FCs reduce instillation frequency as well as total number of doses, treatment complexity and exposure to preservatives. They decrease adverse events and improve adherence.

• Established FCs exhibit a safety and tolerability profile similar, or better to the concomitant use of their constituents. With emerging FCs clinical vigilance is warranted for more rare adverse events that might appear with longer term use even in patients who demonstrate initially good tolerance. The adverse event profile of new FCs requires further investigation.

• Preservative-free FC formulations may potentially improve long-term safety, tolerability and the success of stepwise medical therapy and will gain a greater market share in the future.

• The issue of drug-drug interactions with different IOP-lowering FCs and between various anti-glaucoma drugs requires further elucidation.

• Employing FC options is only one step in the delivery of successful lifelong medical therapy. A better understanding of the safety and tolerability profile of FCs could enhance their use and the outcome of glaucoma therapy worldwide.

This box summarizes key points contained in the article.

Acknowledgments

No writing, editorial or other assistance was used in the preparation of this article.

Author contributions

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Declaration of interest

AG Konstas: Research funding from Allergan, Bayer and Santen; travel support from Vianex; honoraria from Allergan, Mundipharma, Santen and Vianex. G Holló: Consultant for Aerie and Santen, speaker fees from Aerie, Santen, Mundipharma. A Katsanos: Research funding from Laboratoires Théa, congress expenses/speaker fees from Santen, Vianex, Cooper, Bausch & Lomb. P Denis: Allergan, Alcon, Bausch & Lomb, Thea, Santen, iStar, Iridex. L Quaranta: Honoraria and consultancy from Allergan, Novartis, Omikron, Santen, Visufarma. MA Castejón: Grant support from Alcon Vision, Laboratoires Théa, CareGroup, Novartis, Johnson & Johnson Surgical Vision; lecture fees from Alcon Vision, Allergan, CareGroup, Novartis, Santen, Glaukos. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

No funding or sponsorship was received for this study, or publication of this article.